Models of effectiveness of interventions against malaria transmitted by Anopheles albimanus.

BACKGROUND: Most impact prediction of malaria vector control interventions has been based on African vectors. Anopheles albimanus, the main vector in Central America and the Caribbean, has higher intrinsic mortality, is more zoophilic and less likely to rest indoors. Therefore, relative impact among interventions may be different. Prioritizing interventions, in particular for eliminating Plasmodium falciparum from Haiti, should consider local vector characteristics. METHODS: Field bionomics data of An. albimanus from Hispaniola and intervention effect data from southern Mexico were used to parameterize mathematical malaria models. Indoor residual spraying (IRS), insecticide-treated nets (ITNs), and house-screening were analysed by inferring their impact on the vectorial capacity in a difference-equation model. Impact of larval source management (LSM) was assumed linear with coverage. Case management, mass drug administration and vaccination were evaluated by estimating their effects on transmission in a susceptible-infected-susceptible model. Analogous analyses were done for Anopheles gambiae parameterized with data from Tanzania, Benin and Nigeria. RESULTS: While LSM was equally effective against both vectors, impact of ITNs on transmission by An. albimanus was much lower than for An. gambiae. Assuming that people are outside until bedtime, this was similar for the impact of IRS with dichlorodiphenyltrichloroethane (DDT) or bendiocarb, and impact of IRS was less than that of ITNs. However, assuming people go inside when biting starts, IRS had more impact on An. albimanus than ITNs. While house-screening had less impact than ITNs or IRS on An. gambiae, it had more impact on An. albimanus than ITNs or IRS. The impacts of chemoprevention and chemotherapy were comparable in magnitude to those of strategies against An. albimanus. Chemo-prevention impact increased steeply as coverage approached 100%, whilst clinical-case management impact saturated because of remaining asymptomatic infections. CONCLUSIONS: House-screening and repellent IRS are potentially highly effective against An. albimanus if people are indoors during the evening. This is consistent with historical impacts of IRS with DDT, which can be largely attributed to excito-repellency. It also supports the idea that housing improvements have played a critical role in malaria control in North America. For elimination planning, impact estimates need to be combined with feasibility and cost-analysis.

Determinants of bed net use conditional on access in population surveys in Ghana.

BACKGROUND: Insecticide-treated nets (ITNs) are one of the most effective and widely available methods for preventing malaria, and there is interest in understanding the complexities of behavioural drivers of non-use among those with access. This analysis evaluated net use behaviour in Ghana by exploring how several household and environmental variables relate to use among Ghanaians with access to a net. METHODS: Survey data from the Ghana 2014 Demographic and Health Survey and the 2016 Malaria Indicator Survey were used to calculate household members' access to space under a net as well as the proportion of net use conditional on access (NUCA). Geospatial information on cluster location was obtained, as well as average humidex, a measure of how hot it feels, for the month each cluster was surveyed. The relationship between independent variables and net use was assessed via beta-binomial regression models that controlled for spatially correlated random effects using non-Gaussian kriging. RESULTS: In both surveys, increasing wealth was associated with decreased net use among those with access in households when compared to the poorest category. In 2014, exposure to messages about bed net use for malaria prevention was associated with increased net use (OR 2.5, 95% CrI 1.5-4.2), as was living in a rural area in both 2014 (OR 2.5, 95% CrI 1.5-4.3) and 2016 (OR 1.6, 95% CrI 1.1-2.3). The number of nets per person was not associated with net use in either survey. Model fit was improved for both surveys by including a spatial random effect for cluster, demonstrating some spatial autocorrelation in the proportion of people using a net. Humidex, electricity in the household and IRS were not associated with NUCA. CONCLUSION: Net use conditional on access is affected by household characteristics and is also spatially-dependent in Ghana. Setting (whether the household was urban or rural) plays a role, with wealthier and more urban households less likely to use nets when they are available. It will likely be necessary in the future to focus on rural settings, urban settings, and wealth status independently, both to better understand predictors of household net use in these areas and to design more targeted interventions to ensure consistent use of vector control interventions that meet specific needs of the population.

Impact of malaria interventions on child mortality in endemic African settings: comparison and alignment between LiST and Spectrum-Malaria model.

BACKGROUND: In malaria-endemic countries, malaria prevention and treatment are critical for child health. In the context of intervention scale-up and rapid changes in endemicity, projections of intervention impact and optimized program scale-up strategies need to take into account the consequent dynamics of transmission and immunity. METHODS: The new Spectrum-Malaria program planning tool was used to project health impacts of Insecticide-Treated mosquito Nets (ITNs) and effective management of uncomplicated malaria cases (CMU), among other interventions, on malaria infection prevalence, case incidence and mortality in children 0-4 years, 5-14 years of age and adults. Spectrum-Malaria uses statistical models fitted to simulations of the dynamic effects of increasing intervention coverage on these burdens as a function of baseline malaria endemicity, seasonality in transmission and malaria intervention coverage levels (estimated for years 2000 to 2015 by the World Health Organization and Malaria Atlas Project). Spectrum-Malaria projections of proportional reductions in under-five malaria mortality were compared with those of the Lives Saved Tool (LiST) for the Democratic Republic of the Congo and Zambia, for given (standardized) scenarios of ITN and/or CMU scale-up over 2016-2030. RESULTS: Proportional mortality reductions over the first two years following scale-up of ITNs from near-zero baselines to moderately higher coverages align well between LiST and Spectrum-Malaria -as expected since both models were fitted to cluster-randomized ITN trials in moderate-to-high-endemic settings with 2-year durations. For further scale-up from moderately high ITN coverage to near-universal coverage (as currently relevant for strategic planning for many countries), Spectrum-Malaria predicts smaller additional ITN impacts than LiST, reflecting progressive saturation. For CMU, especially in the longer term (over 2022-2030) and for lower-endemic settings (like Zambia), Spectrum-Malaria projects larger proportional impacts, reflecting onward dynamic effects not fully captured by LiST. CONCLUSIONS: Spectrum-Malaria complements LiST by extending the scope of malaria interventions, program packages and health outcomes that can be evaluated for policy making and strategic planning within and beyond the perspective of child survival.

Willingness to pay for small solar powered bed net fans: results of a Becker-DeGroot-Marschak auction in Ghana.

BACKGROUND AND METHODS: Long-lasting insecticidal nets (LLINs) are one of the main interventions recommended by the World Health Organization for malaria vector control. LLINs are ineffective if they are not being used. Subsequent to the completion of a cluster randomized cross over trial conducted in rural Greater Accra where participants were provided with the 'Bɔkɔɔ System'-a set of solar powered net fan and light consoles with a solar panel and battery-or alternative household water filters, all trial participants were invited to participate in a Becker-DeGroot-Marschak auction to determine the mean willingness to pay (WTP) for the fan and light consoles and to estimate the demand curve for the units. RESULTS, DISCUSSION AND CONCLUSIONS: Results demonstraed a mean WTP of approximately 55 Cedis (~13 USD). Demand results suggested that at a price which would support full manufacturing cost recovery, a majority of households in the area would be willing to purchase at least one such unit.

The Economic Value of Long-Lasting Insecticidal Nets and Indoor Residual Spraying Implementation in Mozambique.

AbstractMalaria-endemic countries have to decide how much of their limited resources for vector control to allocate toward implementing long-lasting insecticidal nets (LLINs) versus indoor residual spraying (IRS). To help the Mozambique Ministry of Health use an evidence-based approach to determine funding allocation toward various malaria control strategies, the Global Fund convened the Mozambique Modeling Working Group which then used JANUS, a software platform that includes integrated computational economic, operational, and clinical outcome models that can link with different transmission models (in this case, OpenMalaria) to determine the economic value of vector control strategies. Any increase in LLINs (from 80% baseline coverage) or IRS (from 80% baseline coverage) would be cost-effective (incremental cost-effectiveness ratios ≤ $114/disability-adjusted life year averted). However, LLIN coverage increases tend to be more cost-effective than similar IRS coverage increases, except where both pyrethroid resistance is high and LLIN usage is low. In high-transmission northern regions, increasing LLIN coverage would be more cost-effective than increasing IRS coverage. In medium-transmission central regions, changing from LLINs to IRS would be more costly and less effective. In low-transmission southern regions, LLINs were more costly and less effective than IRS, due to low LLIN usage. In regions where LLINs are more cost-effective than IRS, it is worth considering prioritizing LLIN coverage and use. However, IRS may have an important role in insecticide resistance management and epidemic control. Malaria intervention campaigns are not a one-size-fits-all solution, and tailored approaches are necessary to account for the heterogeneity of malaria epidemiology.

The effect of small solar powered 'Bͻkͻͻ' net fans on mosquito net use: results from a randomized controlled cross-over trial in southern Ghana.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are ineffective malaria transmission prevention tools if they are unused. Discomfort due to heat is the most commonly reported reason for not using nets, but this problem is largely unaddressed. With increasing rural electrification and the dropping price of solar power, fans could improve comfort inside nets and be affordable to populations in malaria endemic areas. Here, results are presented from a pilot randomized controlled cross-over study testing the effect of fans on LLIN use. METHODS: Eighty-three households from two rural communities in Greater Accra, Ghana, randomized into three groups, participated in a 10-month cross-over trial. After a screening survey to identify eligible households, all households received new LLINs. BÍ»kͻͻ net fan systems (one fan per member) were given to households in Group 1 and water filters were given to households in Group 2. At mid-point, Group 1 and 2 crossed over interventions. Households in Group 1 and 2 participated in fortnightly surveys on households' practices related to nets, fans and water filters, while households in Group 3 were surveyed only at screening, mid-point and study end. Entomological and weather data were collected throughout the study. Analysis took both 'per protocol' (PP) and 'intention to treat' (ITT) approaches. The mid- and end-point survey data from Group 1 and 2 were analysed using Firth logistic regressions. Fortnightly survey data from all groups were analysed using logistic regressions with random effects. RESULTS: Provision of fans to households appeared to increase net use in this study. Although the increase in net use explained by fans was not significant in the primary analyses (ITT odds ratio 3.24, p > 0.01; PP odds ratio = 1.17, p > 0.01), it was significant in secondary PP analysis (odds ratio = 1.95, p < 0.01). Net use was high at screening and even higher after provision of new LLINs and with follow up. Fan use was 90-100% depending on the fortnightly visit. CONCLUSIONS: This pilot study could not provide definitive evidence that fans increase net use. A larger study with additional statistical power is needed to assess this association across communities with diverse environmental and socio-demographic characteristics.

Perceptions on the effect of small electric fans on comfort inside bed nets in southern Ghana: a qualitative study.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are known to be highly effective in reducing malaria transmission, morbidity and mortality. However, among those owning an LLIN, use rates are often suboptimal. A reported barrier to bed net use is discomfort due to heat. This qualitative study was part of a larger evaluation conducted in communities without electricity in rural Ghana to assess whether 0.8 W solar powered net fans can increase net use. METHODS: Twenty-three key informant interviews with household heads in the study communities in Shai-Osudoku District, southern Ghana, were conducted from July to August 2015. The purpose of the interviews was to obtain insight into perceptions of participants about the net fan system in relation to LLIN use. RESULTS: While all study participants reported using LLINs, with mosquito nuisance prevention as the prime motivation, heat was also mentioned as a key barrier to net use. Respondents appreciated the net fans because they improved comfort inside bed nets. The LED light on the fan stand became the main source of light at night and positively influenced the perception of the intervention as a whole. CONCLUSION: The general acceptance of the net fan system by the study participants highlights the potential of the intervention to improve comfort inside mosquito nets. This, therefore, has a potential to increase bed net use in areas with low access to electricity.

Malaria intervention scale-up in Africa: effectiveness predictions for health programme planning tools, based on dynamic transmission modelling.

BACKGROUND: Scale-up of malaria prevention and treatment needs to continue to further important gains made in the past decade, but national strategies and budget allocations are not always evidence-based. Statistical models were developed summarizing dynamically simulated relations between increases in coverage and intervention impact, to inform a malaria module in the Spectrum health programme planning tool. METHODS: The dynamic Plasmodium falciparum transmission model OpenMalaria was used to simulate health effects of scale-up of insecticide-treated net (ITN) usage, indoor residual spraying (IRS), management of uncomplicated malaria cases (CM) and seasonal malaria chemoprophylaxis (SMC) over a 10-year horizon, over a range of settings with stable endemic malaria. Generalized linear regression models (GLMs) were used to summarize determinants of impact across a range of sub-Sahara African settings. RESULTS: Selected (best) GLMs explained 94-97 % of variation in simulated post-intervention parasite infection prevalence, 86-97 % of variation in case incidence (three age groups, three 3-year horizons), and 74-95 % of variation in malaria mortality. For any given effective population coverage, CM and ITNs were predicted to avert most prevalent infections, cases and deaths, with lower impacts for IRS, and impacts of SMC limited to young children reached. Proportional impacts were larger at lower endemicity, and (except for SMC) largest in low-endemic settings with little seasonality. Incremental health impacts for a given coverage increase started to diminish noticeably at above ~40 % coverage, while in high-endemic settings, CM and ITNs acted in synergy by lowering endemicity. Vector control and CM, by reducing endemicity and acquired immunity, entail a partial rebound in malaria mortality among people above 5 years of age from around 5-7 years following scale-up. SMC does not reduce endemicity, but slightly shifts malaria to older ages by reducing immunity in child cohorts reached. CONCLUSION: Health improvements following malaria intervention scale-up vary with endemicity, seasonality, age and time. Statistical models can emulate epidemiological dynamics and inform strategic planning and target setting for malaria control.

'Nature or nurture': survival rate, oviposition interval, and possible gonotrophic discordance among South East Asian anophelines.

BACKGROUND: Mosquito survival, oviposition interval and gonotrophic concordance are important determinants of vectorial capacity. These may vary between species or within a single species depending on the environment. They may be estimated by examination of the ovaries of host-seeking mosquitoes. METHODS: Landing collections, Furvela tent-trap and CDC light-trap collections were undertaken sequentially in four locations in Cambodia between February 2012 and December 2013 and samples from the collected mosquitoes were dissected to determine parity, sac stage (indicative of time spent prior to returning to feed) and egg stage. RESULTS: A total of 27,876 Anopheles from 15 species or species groups were collected in the four locations and 2883 specimens were dissected. Both the density and predominant species collected varied according to location and trapping method. Five species were dissected in sufficient numbers to allow comparisons between locations. Estimated oviposition interval differed markedly between species but less within species among different locations. Anopheles aconitus had the shortest cycle, which was 3.17 days (95 % CI 3-3.64), and Anopheles barbirostris had the longest cycle, which took four days (95 % CI 3.29-4). Anopheles minimus had a higher sac rate in weeks leading up to a full moon but there was apparently little effect of moon phase on Anopheles dirus. Despite the fact that many of the species occurred at very low densities, there was no evidence of gonotrophic dissociation in any of them, even during sustained hot, dry periods. The principal Cambodian malaria vector, An. dirus, was only common in one location where it was collected in miniature light-traps inside houses. It did not appear to have an exceptional survival rate (as judged by the low average parous rate) or oviposition cycle. CONCLUSIONS: Differences in the oviposition interval were more pronounced among species within locations than within species among ecologically diverse locations. A nationwide survey using CDC light-traps for the collection of An. dirus inside houses may help in determining patterns of malaria transmission in Cambodia.

Distribution of malaria exposure in endemic countries in Africa considering country levels of effective treatment.

BACKGROUND: Malaria prevalence, clinical incidence, treatment, and transmission rates are dynamically interrelated. Prevalence is often considered a measure of malaria transmission, but treatment of clinical malaria reduces prevalence, and consequently also infectiousness to the mosquito vector and onward transmission. The impact of the frequency of treatment on prevalence in a population is generally not considered. This can lead to potential underestimation of malaria exposure in settings with good health systems. Furthermore, these dynamical relationships between prevalence, treatment, and transmission have not generally been taken into account in estimates of burden. METHODS: Using prevalence as an input, estimates of disease incidence and transmission [as the distribution of the entomological inoculation rate (EIR)] for Plasmodium falciparum have now been made for 43 countries in Africa using both empirical relationships (that do not allow for treatment) and OpenMalaria dynamic micro-simulation models (that explicitly include the effects of treatment). For each estimate, prevalence inputs were taken from geo-statistical models fitted for the year 2010 by the Malaria Atlas Project to all available observed prevalence data. National level estimates of the effectiveness of case management in treating clinical attacks were used as inputs to the estimation of both EIR and disease incidence by the dynamic models. RESULTS AND CONCLUSIONS: When coverage of effective treatment is taken into account, higher country level estimates of average EIR and thus higher disease burden, are obtained for a given prevalence level, especially where access to treatment is high, and prevalence relatively low. These methods provide a unified framework for comparison of both the immediate and longer-term impacts of case management and of preventive interventions.

Do holes in long-lasting insecticidal nets compromise their efficacy against pyrethroid resistant Anopheles gambiae and Culex quinquefasciatus? Results from a release-recapture study in experimental huts.

BACKGROUND: Resistance of malaria vectors to pyrethroids threatens the effectiveness of long-lasting insecticidal nets (LLINs) as a tool for malaria control. Recent experimental hut and observational studies in Benin show that pyrethroid resistance reduces the insecticidal effect and personal protection of LLINs especially when they become torn. The World Health Organization has proposed a threshold for when nets are "too torn" at 1,000 cm(2) for rectangular holes and 790 cm(2) for round holes. This study examines whether there is a threshold above which LLINs no longer reduce malaria transmission. METHODS: Intact and artificially-holed LLINs under three months old and untreated nets were tested by releasing mosquitoes from a susceptible Anopheles gambiae colony, a pyrethroid-resistant An. gambiae population and a resistant Culex quinquefasciatus population in closed experimental huts in Southern Benin, West Africa. The efficacy of LLINs and untreated nets was evaluated in terms of protection against blood feeding, insecticidal effect and potential effect on malaria transmission. RESULTS: Personal protection by both LLINs and untreated nets decreased exponentially with increasing holed surface area, without evidence for a specific threshold beyond which LLINs could be considered as ineffective. The insecticidal effect of LLINs was lower in resistant mosquitoes than in susceptible mosquitoes, but holed surface area had little or no impact on the insecticidal effect of LLINs. LLINs with 22,500 cm(2) holed surface area and target insecticide content provided a personal protection of 0.60 (95 % CI 0.44-0.73) and a low insecticidal effect of 0.20 (95 % CI 0.12-0.30) against resistant An. gambiae. Nevertheless, mathematical models suggested that if 80 % of the population uses such nets, they could still prevent 94 % (95 % CI 89-97 %) of transmission by pyrethroid-resistant An. gambiae. CONCLUSIONS: Even though personal protection by LLINs against feeding mosquitoes is strongly reduced by holes, the insecticidal effect of LLINs is independent of the holed surface area, but strongly dependent on insecticide resistance. Badly torn nets that still contain insecticide have potential to reduce malaria transmission. The relationship between LLIN integrity and efficacy needs to be understood in order to guide LLIN distribution policy.

Applications and limitations of Centers for Disease Control and Prevention miniature light traps for measuring biting densities of African malaria vector populations: a pooled-analysis of 13 comparisons with human landing catches.

BACKGROUND: Measurement of densities of host-seeking malaria vectors is important for estimating levels of disease transmission, for appropriately allocating interventions, and for quantifying their impact. The gold standard for estimating mosquito-human contact rates is the human landing catch (HLC), where human volunteers catch mosquitoes that land on their exposed body parts. This approach necessitates exposure to potentially infectious mosquitoes, and is very labour intensive. There are several safer and less labour-intensive methods, with Centers for Disease Control light traps (LT) placed indoors near occupied bed nets being the most widely used. METHODS: This paper presents analyses of 13 studies with paired mosquito collections of LT and HLC to evaluate these methods for their consistency in sampling indoor-feeding mosquitoes belonging to the two major taxa of malaria vectors across Africa, the Anopheles gambiae sensu lato complex and the Anopheles funestus s.l. group. Both overall and study-specific sampling efficiencies of LT compared with HLC were computed, and regression methods that allow for the substantial variations in mosquito counts made by either method were used to test whether the sampling efficacy varies with mosquito density. RESULTS: Generally, LT were able to collect similar numbers of mosquitoes to the HLC indoors, although the relative sampling efficacy, measured by the ratio of LT:HLC varied considerably between studies. The overall best estimate for An. gambiae s.l. was 1.06 (95% credible interval: 0.68-1.64) and for An. funestus s.l. was 1.37 (0.70-2.68). Local calibration exercises are not reproducible, since only in a few studies did LT sample proportionally to HLC, and there was no geographical pattern or consistent trend with average density in the tendency for LT to either under- or over-sample. CONCLUSIONS: LT are a crude tool at best, but are relatively easy to deploy on a large scale. Spatial and temporal variation in mosquito densities and human malaria transmission exposure span several orders of magnitude, compared to which the inconsistencies of LT are relatively small. LT, therefore, remain an invaluable and safe alternative to HLC for measuring indoor malaria transmission exposure in Africa.

Micro-encapsulated pirimiphos-methyl shows high insecticidal efficacy and long residual activity against pyrethroid-resistant malaria vectors in central Côte d'Ivoire.

BACKGROUND: The wide-scale implementation of insecticide-treated nets and indoor residual spraying (IRS) has contributed to a considerable decrease of malaria morbidity and mortality in sub-Saharan Africa over the last decade. Due to increasing resistance in Anopheles gambiae sensu lato mosquitoes to dichlorodiphenyl trichloroethane (DDT) and pyrethroids, alternative insecticide formulations for IRS with long-lasting residual activity are required to sustain the gains obtained in most malaria-endemic countries. METHODS: Three experimental capsule suspension (CS) formulations of the organophosphate pirimiphos-methyl were evaluated together with Actellic 50 EC, an emulsifiable concentrate (EC) of pirimiphos-methyl, and the pyrethroid ICON 10 CS, a lambda-cyhalothrin CS formulation, in an experimental hut trial. The formulations were tested on two types of surfaces: mud and cement. The study with a 12-month follow-up was carried out in Bouaké, central Côte d'Ivoire, where An. gambiae mosquitoes show high levels of resistance against pyrethroids, DDT and carbamates. Residual activity was also tested in cone bioassays with the susceptible An. gambiae KISUMU strain. RESULTS: One of the CS formulations of pirimiphos-methyl, CS BM, outperformed all other formulations tested. On cement surfaces, the odds ratios of overall insecticidal effect on An. gambiae s.l. of pirimiphos-methyl CS BM compared to Actellic 50 EC were 1.4 (95% confidence interval (CI): 1.2-1.7) for the first three months, 5.6 (95% CI: 4.4-7.2) for the second three months, and 3.6 (95% CI: 3.0-4.4) for the last six months of follow-up. On mud surfaces, the respective odds ratios were 2.5 (95% CI: 1.9-3.3), 3.5 (95% CI: 2.7-4.5), and 1.7 (95% CI: 1.4-2.2). On cement, the residual activity of pirimiphos-methyl CS BM measured using cone tests was similar to that of lambda-cyhalothrin and for both treatments, mortality of susceptible Kisumu laboratory strain was not significantly below the World Health Organization pre-set threshold of 80% for 30 weeks after spraying. Residual activity was shorter on mud surfaces, mortality falling below 80% on both pirimiphos-methyl CS BM and lambda-cyhalothrin treated surfaces at 25 weeks post-treatment. CONCLUSION: CS formulations of pirimiphos-methyl are promising alternatives for IRS, as they demonstrate prolonged insecticidal effect and residual activity against malaria mosquitoes.

Evidence of an 'invitation' effect in feeding sylvatic Stegomyia albopicta from Cambodia.

BACKGROUND: Orientation of haematophagous insects towards a potential host is largely mediated by kairomones that, in some groups or species may include chemicals produced during feeding by the insects themselves, the so called 'invitation' effect. METHODS: The 'invitation' effect in blood-feeding diurnally active Stegomyia albopicta was investigated over 33 days in secondary forest in Mondolkiri Province, Cambodia. Two human volunteers sitting inside a shelter collected mosquitoes and noted where and when they landed. A 10% emanator of a synthetic pyrethroid with high vapour action was in use on alternate days. RESULTS: Overall, 2726 mosquitoes were collected, 1654 of which had the landing site recorded. The heads of the volunteers were the locations with the highest density of landings per surface area whilst the knees and elbows accounted for most of the landings received on the arms and legs. Landings recorded within three minutes of each other on a collector were about 2.5 times more likely to be on the same body part than on a random body part, weighted for landing site preference. This preference did not vary with collector or pyrethroid. CONCLUSIONS: The 'invitation' effect may be due to a semio-chemical produced early in the feeding process. Incorporation of such a chemical into traps designed to control this important vector of dengue and chikungunya viruses might potentially improve their attractiveness.

Clustering of vector control interventions has important consequences for their effectiveness: a modelling study.

Vector control interventions have resulted in considerable reductions in malaria morbidity and mortality. When universal coverage cannot be achieved for financial or logistical reasons, the spatial arrangement of vector control is potentially important for optimizing benefits. This study investigated the effect of spatial clustering of vector control interventions on reducing the population of biting mosquitoes. A discrete-space continuous-time mathematical model of mosquito population dynamics and dispersal was extended to incorporate vector control interventions of insecticide treated bednets (ITNs), Indoor residual Spraying (IRS), and larviciding. Simulations were run at varying levels of coverage and degree of spatial clustering. At medium to high coverage levels of each of the interventions or in combination was more effective to spatially spread these interventions than to cluster them. Suggesting that when financial resources are limited, unclustered distribution of these interventions is more effective. Although it is often stated that locally high coverage is needed to achieve a community effect of ITNs or IRS, our results suggest that if the coverage of ITNs or IRS are insufficient to achieve universal coverage, and there is no targeting of high risk areas, the overall effects on mosquito densities are much greater if they are distributed in an unclustered way, rather than clustered in specific localities. Also, given that interventions are often delivered preferentially to accessible areas, and are therefore clustered, our model results show this may be inefficient. This study provides evidence that the effectiveness of an intervention can be highly dependent on its spatial distribution. Vector control plans should consider the spatial arrangement of any intervention package to ensure effectiveness is maximized.

Effects of changing mosquito host searching behaviour on the cost effectiveness of a mass distribution of long-lasting, insecticidal nets: a modelling study.

BACKGROUND: The effectiveness of long-lasting, insecticidal nets (LLINs) in preventing malaria is threatened by the changing biting behaviour of mosquitoes, from nocturnal and endophagic to crepuscular and exophagic, and by their increasing resistance to insecticides. METHODS: Using epidemiological stochastic simulation models, we studied the impact of a mass LLIN distribution on Plasmodium falciparum malaria. Specifically, we looked at impact in terms of episodes prevented during the effective life of the batch and in terms of net health benefits (NHB) expressed in disability adjusted life years (DALYs) averted, depending on biting behaviour, resistance (as measured in experimental hut studies), and on pre-intervention transmission levels. RESULTS: Results were very sensitive to assumptions about the probabilistic nature of host searching behaviour. With a shift towards crepuscular biting, under the assumption that individual mosquitoes repeat their behaviour each gonotrophic cycle, LLIN effectiveness was far less than when individual mosquitoes were assumed to vary their behaviour between gonotrophic cycles. LLIN effectiveness was equally sensitive to variations in host-searching behaviour (if repeated) and to variations in resistance. LLIN effectiveness was most sensitive to pre-intervention transmission level, with LLINs being least effective at both very low and very high transmission levels, and most effective at around four infectious bites per adult per year. A single LLIN distribution round remained cost effective, except in transmission settings with a pre-intervention inoculation rate of over 128 bites per year and with resistant mosquitoes that displayed a high proportion (over 40%) of determined crepuscular host searching, where some model variants showed negative NHB. CONCLUSIONS: Shifts towards crepuscular host searching behaviour can be as important in reducing LLIN effectiveness and cost effectiveness as resistance to pyrethroids. As resistance to insecticides is likely to slow down the development of behavioural resistance and vice versa, the two types of resistance are unlikely to occur within the same mosquito population. LLINs are likely cost effective interventions against malaria, even in areas with strong resistance to pyrethroids or where a large proportion of host-mosquito contact occurs during times when LLIN users are not under their nets.

Generalized seasonal autoregressive integrated moving average models for count data with application to malaria time series with low case numbers.

INTRODUCTION: With the renewed drive towards malaria elimination, there is a need for improved surveillance tools. While time series analysis is an important tool for surveillance, prediction and for measuring interventions' impact, approximations by commonly used Gaussian methods are prone to inaccuracies when case counts are low. Therefore, statistical methods appropriate for count data are required, especially during "consolidation" and "pre-elimination" phases. METHODS: Generalized autoregressive moving average (GARMA) models were extended to generalized seasonal autoregressive integrated moving average (GSARIMA) models for parsimonious observation-driven modelling of non Gaussian, non stationary and/or seasonal time series of count data. The models were applied to monthly malaria case time series in a district in Sri Lanka, where malaria has decreased dramatically in recent years. RESULTS: The malaria series showed long-term changes in the mean, unstable variance and seasonality. After fitting negative-binomial Bayesian models, both a GSARIMA and a GARIMA deterministic seasonality model were selected based on different criteria. Posterior predictive distributions indicated that negative-binomial models provided better predictions than Gaussian models, especially when counts were low. The G(S)ARIMA models were able to capture the autocorrelation in the series. CONCLUSIONS: G(S)ARIMA models may be particularly useful in the drive towards malaria elimination, since episode count series are often seasonal and non-stationary, especially when control is increased. Although building and fitting GSARIMA models is laborious, they may provide more realistic prediction distributions than do Gaussian methods and may be more suitable when counts are low.

A novel approach for measuring the burden of uncomplicated Plasmodium falciparum malaria: application to data from Zambia.

Measurement of malaria burden is fraught with complexity, due to the natural history of the disease, delays in seeking treatment or failure of case management. Attempts to establish an appropriate case definition for a malaria episode has often resulted in ambiguities and challenges because of poor information about treatment seeking, patterns of infection, recurrence of fever and asymptomatic infection. While the primary reason for treating malaria is to reduce disease burden, the effects of treatment are generally ignored in estimates of the burden of malaria morbidity, which are usually presented in terms of numbers of clinical cases or episodes, with the main data sources being reports from health facilities and parasite prevalence surveys. The use of burden estimates that do not consider effects of treatment, leads to under-estimation of the impact of improvements in case management. Official estimates of burden very likely massively underestimate the impact of the roll-out of ACT as first-line therapy across Africa. This paper proposes a novel approach for estimating burden of disease based on the point prevalence of malaria attributable disease, or equivalently, the days with malaria fever in unit time. The technique makes use of data available from standard community surveys, analyses of fever patterns in malaria therapy patients, and data on recall bias. Application of this approach to data from Zambia for 2009-2010 gave an estimate of 2.6 (95% credible interval: 1.5-3.7) malaria attributable fever days per child-year. The estimates of recall bias, and of the numbers of days with illness contributing to single illness recalls, could be applied more generally. To obtain valid estimates of the overall malaria burden using these methods, there remains a need for surveys to include the whole range of ages of hosts in the population and for data on seasonality patterns in confirmed case series.

Effects of pyrethroid resistance on the cost effectiveness of a mass distribution of long-lasting insecticidal nets: a modelling study.

BACKGROUND: The effectiveness of insecticide-treated nets in preventing malaria is threatened by developing resistance against pyrethroids. Little is known about how strongly this affects the effectiveness of vector control programmes. METHODS: Data from experimental hut studies on the effects of long-lasting, insecticidal nets (LLINs) on nine anopheline mosquito populations, with varying levels of mortality in World Health Organization susceptibility tests, were used to parameterize malaria models. Both simple static models predicting population-level insecticidal effectiveness and protection against blood feeding, and complex dynamic epidemiological models, where LLINs decayed over time, were used. The epidemiological models, implemented in OpenMalaria, were employed to study the impact of a single mass distribution of LLINs on malaria, both in terms of episodes prevented during the effective lifetime of the batch of LLINs, and in terms of net health benefits (NHB) expressed in disability-adjusted life years (DALYs) averted during that period, depending on net type (standard pyrethroid-only LLIN or pyrethroid-piperonyl butoxide combination LLIN), resistance status, coverage and pre-intervention transmission level. RESULTS: There were strong positive correlations between insecticide susceptibility status and predicted population level insecticidal effectiveness of and protection against blood feeding by LLIN intervention programmes. With the most resistant mosquito population, the LLIN mass distribution averted up to about 40% fewer episodes and DALYs during the effective lifetime of the batch than with fully susceptible populations. However, cost effectiveness of LLINs was more sensitive to the pre-intervention transmission level and coverage than to susceptibility status. For four out of the six Anopheles gambiae sensu lato populations where direct comparisons between standard LLINs and combination LLINs were possible, combination nets were more cost effective, despite being more expensive. With one resistant population, both net types were equally effective, and with one of the two susceptible populations, standard LLINs were more cost effective. CONCLUSION: Despite being less effective when compared to areas with susceptible mosquito populations, standard and combination LLINs are likely to (still) be cost effective against malaria even in areas with strong pyrethroid resistance. Combination nets are likely to be more cost effective than standard nets in areas with resistant mosquito populations.

Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden.

BACKGROUND: Past experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT) is preferred to mass drug administration (MDA), as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease) and access to case management. METHODS: MSAT incremental cost-effectiveness ratios (ICERs) were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN) coverage in each baseline health system, in the absence of MSAT. RESULTS: MSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR) of two infectious bites per adult per annum (IBPAPA) MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs) of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further. CONCLUSIONS: In all the transmission settings considered, achieving a minimal level of ITN coverage is a "best buy". At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage. If undertaken as a burden-reducing intervention, MSAT should be continued indefinitely and should complement, not replace, case management and vector control interventions.